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https://www.readbyqxmd.com/read/28107775/beta-caryophyllene-protects-against-alcoholic-steatohepatitis-by-attenuating-inflammation-and-metabolic-dysregulation-in-mice
#1
Zoltan V Varga, Csaba Matyas, Katalin Erdelyi, Resat Cinar, Daniela Nieri, Andrea Chicca, Balazs Tamas Nemeth, Janos Paloczi, Tamas Lajtos, Lukas Corey, Gyorgy Hasko, Bin Gao, George Kunos, Jürg Gertsch, Pal Pacher
BACKGROUND AND AIMS: Beta-caryophyllene (BCP) is a plant-derived FDA approved food additive with anti-inflammatory properties. Some of its beneficial effects in vivo reported to involve activation of cannabinoid 2 receptors (CB2) that are predominantly expressed in immune cells. Herein, we evaluated the translational potential of BCP using a well-established model of chronic and binge alcohol-induced liver injury. METHODS: In this study we investigated the effects of BCP on liver injury induced by chronic plus binge alcohol feeding in mice in vivo by using biochemical assays, real-time PCR and histology analyses...
January 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28107544/cutaneous-hpv8-and-mmupv1-e6-proteins-target-the-notch-and-tgf-%C3%AE-tumor-suppressors-to-inhibit-differentiation-and-sustain-keratinocyte-proliferation
#2
Jordan M Meyers, Aayushi Uberoi, Miranda Grace, Paul F Lambert, Karl Munger
Cutaneous beta-papillomaviruses are associated with non-melanoma skin cancers that arise in patients who suffer from a rare genetic disorder, Epidermodysplasia verruciformis (EV) or after immunosuppression following organ transplantation. Recent studies have shown that the E6 proteins of the cancer associated beta human papillomavirus (HPV) 5 and HPV8 inhibit NOTCH and TGF-β signaling. However, it is unclear whether disruption of these pathways may contribute to cutaneous HPV pathogenesis and carcinogenesis...
January 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28107503/osteopontin-affects-insulin-vesicle-localization-and-ca2-homeostasis-in-pancreatic-beta-cells-from-female-mice
#3
Anna Wendt, Inês G Mollet, Anki Knutsson, Victor S Bolmgren, Anna Hultgårdh-Nilsson, Maria F Gomez, Lena Eliasson
Type 2 diabetic patients suffer from insulin resistance and reduced insulin secretion. Osteopontin (OPN), a versatile protein expressed in several tissues throughout the body including the islets of Langerhans, has previously been implicated in the development of insulin resistance. Here we have investigated the role of OPN in insulin secretion using an OPN knock out mouse model (OPN-/-). Ultra-structural analyzes of islets from OPN-/- and WT mice indicated weaker cell-cell connections between the islet cells in the OPN-/- mouse compared to WT...
2017: PloS One
https://www.readbyqxmd.com/read/28106991/discovery-of-a-phosphoinositide-3-kinase-pi3k-b-d-inhibitor-for-the-treatment-of-phosphatase-and-tensin-homolog-pten-deficient-tumors-building-pi3kb-potency-in-a-pi3kd-selective-template-by-targeting-non-conserved-asp856
#4
Stéphane Perreault, Jayaraman Chandrasekhar, Zhi-Hua Cui, Jerry B Evarts, Jia Hao, Joshua A Kaplan, Adam Kashishian, Kathleen S Keegan, Thomas Kenney, David J Koditek, Latesh Lad, Eve-Irene Lepist, Mary E McGrath, Leena Patel, Bart Phillips, Joseph Therrien, Jennifer Treiberg, Anella Yahiaoui, Gary Phillips
Phosphoinositide 3-kinase (PI3K) beta signaling is required to sustain cancer cell growth in which the tumor suppressor phosphatase and tensin homolog (PTEN) has been deactivated. This manuscript describes the discovery, optimization, and in vivo evaluation of a novel series of PI3Kbeta/delta inhibitors in which PI3Kbeta potency was built in a PI3Kdelta-selective template. This work led to the discovery of a highly selective PI3Kbeta/delta inhibitor displaying excellent pharmacokinetic profile and efficacy in a human PTEN-deficient LNCaP prostate carcinoma xenograft tumor model...
January 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28106247/validation-of-the-nccn-ipi-for-diffuse-large-b-cell-lymphoma-dlbcl-the-addition-of-%C3%AE-2-microglobulin-yields-a-more-accurate-geltamo-ipi
#5
Carlos Montalbán, Antonio Díaz-López, Ivan Dlouhy, Jordina Rovira, Armando Lopez-Guillermo, Sara Alonso, Alejandro Martín, Juan M Sancho, Olga García, Jose M Sánchez, Mario Rodríguez, Silvana Novelli, Antonio Salar, Antonio Gutiérrez, Maria J Rodríguez-Salazar, Mariana Bastos, Juan F Domínguez, Rubén Fernández, Sonia Gonzalez de Villambrosia, José A Queizan, Raul Córdoba, Raquel de Oña, Andrés López-Hernandez, Julian M Freue, Heidys Garrote, Lourdes López, Ana M Martin-Moreno, Jose Rodriguez, Víctor Abraira, Juan F García
The study included 1848 diffuse large B-cell lymphoma (DLBCL)patients treated with chemotherapy/rituximab. The aims were to validate the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) and explore the effect of adding high Beta-2 microglobulin (β2M), primary extranodal presentation and intense treatment to the NCCN-IPI variables in order to develop an improved index. Comparing survival curves, NCCN-IPI discriminated better than IPI, separating four risk groups with 5-year overall survival rates of 93%, 83%, 67% and 49%, but failing to identify a true high-risk population...
January 20, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28106165/effects-of-sr-ht-gahnite-on-osteogenesis-and-angiogenesis-by-adipose-derived-stem-cells-for-critical-sized-calvarial-defect-repair
#6
Guifang Wang, Seyed-Iman Roohani-Esfahani, Wenjie Zhang, Kaige Lv, Guangzheng Yang, Xun Ding, Derong Zou, Daxiang Cui, Hala Zreiqat, Xinquan Jiang
Tissue engineering strategies to construct vascularized bone grafts are now attracting much attention. Strontium-hardystonite-Gahnite (Sr-HT-Gahnite) is a strong, highly porous, and biocompatible calcium silicate based bio-ceramic that contains strontium and zinc ions. Adipose derived stem cells (ASCs) have been demonstrated to have the ability in promoting osteogenesis and angiogenesis. In this study, the effects of Sr-HT-Gahnite on cell morphology, cell proliferation, and osteogenic differentiation of ASCs were systematically investigated...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106117/norovirus-p-particle-based-active-a%C3%AE-immunotherapy-elicits-sufficient-immunogenicity-and-improves-cognitive-capacity-in-a-mouse-model-of-alzheimer-s-disease
#7
Lu Fu, Yingnan Li, Yue Hu, Yayuan Zheng, Bin Yu, Haihong Zhang, Jiaxin Wu, Hui Wu, Xianghui Yu, Wei Kong
Disease-modifying immunotherapies focusing on reducing amyloid-beta (Aβ) deposition are the main treatment for Alzheimer's disease (AD). However, none of the Aβ immunotherapies has produced clinically meaningful results to date. The main reason for this lack of efficacy is that the vaccine induces insufficiently high antibody titers, as it contains small B-cell epitope of Aβ to avoid Aβ42-specific T-cell activation. With the aim of generating a potent AD vaccine, we designed the protein PP-3copy-Aβ1-6-loop123, comprising three copies of Aβ1-6 inserted into three loops of a novel vaccine platform, the norovirus P particle, which could present Aβ at its surface and remarkably enhance the immunogenicity of the vaccine...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105733/vitamin-d-supplementation-for-sickle-cell-disease
#8
REVIEW
Htoo Htoo Kyaw Soe, Adinegara Bl Abas, Nan Nitra Than, Han Ni, Jaspal Singh, Abdul Razzak Bin Mohd Said, Ifeyinwa Osunkwo
BACKGROUND: Sickle cell disease is a genetic chronic haemolytic and pro-inflammatory disorder. The clinical manifestations of sickle cell disease result from the presence of mutations on the beta globin genes that generate an abnormal haemoglobin product (called haemoglobin S) within the red blood cell. Sickle cell disease can lead to many complications such as acute chest syndrome, stroke, acute and chronic bone complications (including painful vaso-occlusive crisis, osteomyelitis, osteonecrosis and osteoporosis)...
January 20, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28104168/meld-and-child-pugh-scores-are-related-to-immune-status-of-intrahepatic-natural-killer-cells-in-liver-transplant-candidates
#9
N Tanimine, Y Tanaka, T Abe, J Piao, K Ishiyama, T Kobayashi, K Ide, M Ohira, H Tahara, S Shimizu, Y Saeki, H Sakai, T Yano, H Ohdan
BACKGROUND: The role and phenotypic alterations of intrahepatic natural killer (NK) cells in liver disease were investigated. Although intrahepatic NK cells reportedly functionally deteriorate in the fibrotic liver, it remains unclear how the clinical severity of liver disease affects intrahepatic NK cells in patients with advanced liver failure. METHODS: We analyzed the phenotypic properties of intrahepatic NK cells by using mononuclear cells extracted from ex vivo liver perfusate effluents from patients who underwent liver transplantation...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28103316/alpha-melanocyte-stimulating-hormone-protects-against-cytokine-induced-barrier-damage-in-caco-2-intestinal-epithelial-monolayers
#10
Judit Váradi, András Harazin, Ferenc Fenyvesi, Katalin Réti-Nagy, Péter Gogolák, György Vámosi, Ildikó Bácskay, Pálma Fehér, Zoltán Ujhelyi, Gábor Vasvári, Eszter Róka, David Haines, Mária A Deli, Miklós Vecsernyés
Alpha-melanocyte-stimulating hormone (α-MSH) is a potent anti-inflammatory peptide with cytoprotective effect in various tissues. The present investigation demonstrates the ability of α-MSH to interact with intestinal epithelial cell monolayers and mitigate inflammatory processes of the epithelial barrier. The protective effect of α-MSH was studied on Caco-2 human intestinal epithelial monolayers, which were disrupted by exposure to tumor necrosis factor-α and interleukin-1β. The barrier integrity was assessed by measuring transepithelial electric resistance (TEER) and permeability for marker molecules...
2017: PloS One
https://www.readbyqxmd.com/read/28103285/radioiodinated-exendin-4-is-superior-to-the-radiometal-labelled-glucagon-like-peptide-1-receptor-probes-overcoming-their-high-kidney-uptake
#11
Tilman Läppchen, Roswitha Tönnesmann, Jos Eersels, Philipp T Meyer, Helmut R Maecke, Svetlana N Rylova
GLP-1 receptors are ideal targets for preoperative imaging of benign insulinoma and for quantifying the beta cell mass. The existing clinical tracers targeting GLP-1R are all agonists with low specific activity and very high kidney uptake. In order to solve those issues we evaluated GLP-1R agonist Ex-4 and antagonist Ex(9-39) radioiodinated at Tyr40 side by side with [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]Ex-4 (68Ga-Ex-4) used in the clinic. The Kd, Bmax, internalization and binding kinetics of [Nle14,125I-Tyr40-NH2]Ex-4 and [Nle14,125I-Tyr40-NH2]Ex(9-39) were studied in vitro using Ins-1E cells...
2017: PloS One
https://www.readbyqxmd.com/read/28103257/activation-of-the-jak-stat-signaling-pathway-after-in-vitro-stimulation-with-ifn%C3%A3-in-multiple-sclerosis-patients-according-to-the-therapeutic-response-to-ifn%C3%A3
#12
Isaac Hurtado-Guerrero, Maria Jesús Pinto-Medel, Patricia Urbaneja, Jose Luis Rodriguez-Bada, Antonio León, Miguel Guerrero, Óscar Fernández, Laura Leyva, Begoña Oliver-Martos
Interferon beta (IFNß) is a common treatment used for multiple sclerosis (MS) which acts through the activation of the JAK-STAT pathway. However, this therapy is not always effective and currently there are no reliable biomarkers to predict therapeutic response. We postulate that the heterogeneity in the response to IFNß therapy could be related to differential activation patterns of the JAK-STAT signaling pathway. Our aim was to evaluate the basal levels and the short term activation of this pathway after IFNß stimulation in untreated and IFNß treated patients, as well as according to therapeutic response...
2017: PloS One
https://www.readbyqxmd.com/read/28102848/statins-in-anthracycline-induced-cardiotoxicity-rac-and-rho-and-the-heartbreakers
#13
REVIEW
Christian Henninger, Gerhard Fritz
Cancer patients receiving anthracycline-based chemotherapy are at risk to develop life-threatening chronic cardiotoxicity with the pathophysiological mechanism of action not fully understood. Besides the most common hypothesis that anthracycline-induced congestive heart failure (CHF) is mainly caused by generation of reactive oxygen species, recent data point to a critical role of topoisomerase II beta (TOP2B), which is a primary target of anthracycline poisoning, in the pathophysiology of CHF. As the use of the only clinically approved cardioprotectant dexrazoxane has been limited by the FDA in 2011, there is an urgent need for alternative cardioprotective measures...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102541/tgf-%C3%AE-regulation-of-encephalitogenic-and-regulatory-t-cells-in-multiple-sclerosis
#14
REVIEW
Priscilla W Lee, Mary E Severin, Amy E Lovett-Racke
Transforming growth factor-beta (TGF-β) is a pleiotropic cytokine that has been shown to influence the differentiation and function of T cells. The role that TGF-β plays in immune-mediated disease, such as multiple sclerosis (MS), has become a major area of investigation since CD4(+) T cells appear to be a major mediator of autoimmunity. This review provides an analysis of the literature on the role that TGF-β plays in the generation and regulation of encephalitogenic and regulatory T cells in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, as well as in T cells of MS patients...
January 19, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28101643/polymorphisms-in-genes-encoding-mir-155-and-mir-146a-are-associated-with-protection-to-type-1-diabetes-mellitus
#15
Taís S Assmann, Guilherme C K Duarte, Letícia A Brondani, Pedro H O de Freitas, Égina M Martins, Luís H Canani, Daisy Crispim
AIMS: Type 1 diabetes mellitus (T1DM) is characterized by severe autoimmune destruction of pancreatic beta-cells. The triggering of autoimmunity against beta-cells is probably caused by a combination of environmental and genetic risk factors. Even though much is known about the genetic of T1DM, more information is needed to completely unravel this tangled disease. MicroRNAs (miRNAs) are a class of small noncoding RNAs molecules that negatively regulate gene expression by inducing target mRNA cleavage or by inhibiting protein translation...
January 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28100873/microrna-10a-targets-t-box-5-to-inhibit-the-development-of-cardiac-hypertrophy
#16
Dan Wang, Guanqun Zhai, Yangfei Ji, Haiyun Jing
The mechanism of cardiac hypertrophy involving microRNAs (miRNAs) is attracting increasing attention. Our study aimed to investigate the role of miR-10a in cardiac hypertrophy development and the underlying regulatory mechanism.Transverse abdominal aortic constriction (TAAC) surgery was performed to establish a cardiac hypertrophy rat model, and angiotensin II (AngII) was used to induce cardiac hypertrophy in cultured neonatal rat cardiomyocytes. Expression of T-box 5 (TBX5) and miR-10a was altered by cell transfection of siRNA or miRNA mimic/inhibitor...
January 17, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28100625/the-ptpn14-tumour-suppressor-is-a-degradation-target-of-human-papillomavirus-e7
#17
Anita Szalmás, Vjekoslav Tomaić, Om Basukala, Paola Massimi, Suruchi Mittal, József Kónya, Lawrence Banks
: Activation of signalling pathways ensuring cell growth are essential for the proliferative competence of human papillomavirus (HPV)-infected cells. Tyrosine kinases and phosphatases are key regulators of cellular growth control pathways. A recently identified potential cellular target of HPV E7 is the cytoplasmic protein tyrosine phosphatase PTPN14, which is a potential tumour suppressor and is linked to the control of the Hippo and Wnt/beta-catenin signalling pathways. In this study we show that the E7 proteins of both high-risk and low-risk mucosal HPV types can interact with PTPN14...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100270/pro-inflammation-nf-%C3%AE%C2%BAb-signaling-triggers-a-positive-feedback-via-enhancing-cholesterol-accumulation-in-liver-cancer-cells
#18
Mingyan He, Wenhui Zhang, Yinying Dong, Lishun Wang, Tingting Fang, Wenqing Tang, Bei Lv, Guanglang Chen, Biwei Yang, Peixin Huang, Jinglin Xia
BACKGROUND: Hepatocellular carcinoma (HCC) develops in a complex microenvironment characterized by chronic inflammation. In recent years, cholesterol metabolic abnormalities have been implicated the importance in cancer cell physiology. This study was designed to investigate the relationship between inflammation and cholesterol accumulation in HCC cells. METHODS: Human HCC cells HepG2 and Huh7 were cultured and stimulated with lipopolysaccharide (LPS) for 24 h...
January 18, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28099600/dhea-and-frontal-fibrosing-alopecia-molecular-and-physiopathological-mechanisms
#19
Neide Kalil Gaspar
The transforming growth factor-beta 1 (TGFβ1) promotes fibrosis, differentiating epithelial cells and quiescent fibroblasts into myofibroblasts and increasing expression of extracellular matrix. Recent investigations have shown that PPAR (peroxisome proliferator-activated receptor*) is a negative regulator of fibrotic events induced by TGFβ1. Dehydroepiandrosterone (DHEA) is an immunomodulatory hormone essential for PPAR functions, and is reduced in some processes characterized by fibrosis. Although scarring alopecia characteristically develops in the female biological period in which occurs decreased production of DHEA, there are no data in the literature relating its reduction to fibrogenic process of this condition...
November 2016: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/28099381/daily-propranolol-administration-reduces-persistent-injury-associated-anemia-following-severe-trauma-and-chronic-stress
#20
Ines G Alamo, Kolenkode B Kannan, Letitia E Bible, Tyler J Loftus, Harry Ramos, Philip A Efron, Alicia M Mohr
BACKGROUND: Following severe trauma, patients develop a norepinephrine-mediated persistent, injury-associated anemia. This anemia is associated with suppression of bone marrow erythroid colony growth, along with decreased iron levels, and elevated erythropoietin (EPO) levels, which are insufficient to promote effective erythropoiesis. The impact of norepinephrine on iron regulators such as ferroportin, transferrin and transferrin receptor-1 (TFR-1) are unknown. Using a clinically relevant rodent model of lung contusion (LC), hemorrhagic shock (HS), and chronic stress (CS), we hypothesize that daily propranolol (BB), a non-selective beta-blocker, restores bone marrow function and improves iron homeostasis...
January 17, 2017: Journal of Trauma and Acute Care Surgery
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